The most recent results from the MTA and PATS found that daily stimulant therapy with a 12 hour methylphenidate (MPH) regimen produced sustained growth deficits. In the MTA, there was as 1.7 inch difference in subjects medicated before and during the MTA vs. those never medicated. This difference persisted as long as medication was used, out to age 18. In PATS, one year of stimulant treatment at conservative doses produced a 20% reduction in expected height gain. This deceleration continued almost unabated over the next two years of medication use. Hence, there now appears to be evidence of concerning and persistent stimulant-induced growth suppression (SIGS). There were two major limitations of these findings. First, both used short acting stimulants, which are no longer the standard of care for pediatric ADHD. Extended release (ER) stimulants are the treatment of choice, but their longer therapeutic effects and ease of use may increase the chances of weight loss. Second was the failure to keep children in their assigned treatment cells past 14 months, thereby losing the effects of random assignment. In addition, anorexia and weight loss are two of the most commonly experienced adverse events with stimulants and are the side effects most likely to lead to treatment discontinuation. For a daily treatment, adherence is critical for success, and drug tolerability is a significant predictor of adherence. Even before PATS and the MTA, there was sizable stigma over the use of stimulants for ADHD, largely due to concerns about their long term safety in children. For these reasons, it is imperative to precisely estimate the risks of SIGS, examine the underlying mechanisms and develop treatments for it. While drug holidays and caloric supplementation are two common treatments for SIGS, there has been little systematic investigation of either. It is unknown if they are effective or feasible. Therefore, using a randomized adaptive design, we will evaluate the efficacy and feasibility of these two practices vs. routine monitoring of growth in 180 prepubertal children with ADHD. The study will address the limitations of prior work by using an ER MPH product and by keeping subjects in their assigned cells for 30 months. An additional 50 subjects will be treated solely with behavioral therapies to evaluate for growth abnormalities associated with ADHD. The study will assess will the risk of SIGS with ER stimulants and the underlying mechanisms while providing evidenced-based treatments for its management. Weight loss is a common side effect experienced by many of the millions of school-aged children prescribed stimulants that can lead to discontinuation of treatment. Now, there is evidence from PATS and the MTA that stimulants can lead to sustained and concerning growth suppression in children continuously treated with them throughout their childhood. This study holds substantial public health benefit as it will be the first randomized controlled trial for the treatment of stimulant induced growth suppression. In addition, it will enhance the understanding of growth abnormalities associated with ADHD vs. those secondary to persistent use of extended release stimulants as well as the mechanisms behind stimulant induced growth suppression. PUBLIC HEALTH RELEVANCE: Weight loss is a common side effect experienced by many of the millions of school-aged children prescribed stimulants that can lead to discontinuation of treatment. Now, there is evidence from PATS and the MTA that stimulants can lead to sustained and concerning growth suppression in children continuously treated with them throughout their childhood. This study holds substantial public health benefit as it will be the first randomized controlled trial for the treatment of stimulant induced growth suppression. In addition, it will enhance the understanding of growth abnormalities associated with ADHD vs. those secondary to persistent use of extended release stimulants as well as the mechanisms behind stimulant induced growth suppression.